(PQC3) Using an Immunoscore to Assess Tumor-medicated Immune Variations in African -American

描述（由申请人提供）：尽管有大量证据表明肿瘤介导的免疫反应对前列腺癌患者预后的重要性，但没有研究充分评估非裔美国患者肿瘤介导的免疫反应。鉴于非裔美国人种族是更具侵袭性和致死性前列腺癌的危险因素，本研究的目的是检验前列腺中肿瘤浸润淋巴细胞的数量和定位差异与前列腺种族健康差异相关的总体假设，以及雄激素信号调节这一过程。在本研究中，我们将利用2003年至2013年间收集的前列腺组织生物库，其中包含超过6,500份档案前列腺癌标本，其中25%（1,630）来自非洲裔美国男性。为了更明确地验证我们的假设，我们将使用“免疫评分”的概念。免疫评分是一种基于肿瘤中CD3+和CD8+ T淋巴细胞定量的综合评分，已经被发现是结直肠癌患者的一个强有力的预测指标，而对其他实体肿瘤类型的探索才刚刚开始。在

DESCRIPTION (provided by applicant): Despite a body of evidence demonstrating the importance of the tumor-mediated immune response to the outcome of prostate cancer patients, no studies have adequately evaluated the tumor-mediated immune response in African American patients. Given that the African American race is a risk factor for more aggressive and lethal prostate cancer, the purpose of this study is to test the overall hypothesis that difference in the quantity and localization of tumor-infiltrating lymphocytes into the prostate gland correlat with PCa racial health disparities and that androgen signaling regulates this process. For this study, we will utilize a prostate tissue biorepository collected between 2003 and 2013, containing over 6,500 archival prostate cancer specimens, 25% (1,630) of which are from African American men. To test our hypothesis in a definitive way, we will utilize the concept of an "immunoscore." The immunoscore, a combined score based on the quantitation of CD3+ and CD8+ T lymphocytes in a tumor, has already been found to be a strong predictive indicator in patients with colorectal cancer and is only starting to be explored for other solid tumor types. In our Specific Aim 1, we will adapt existing immunoscoring methodology to be compatible with and applicable to prostate cancer, and will test the reproducibility and robustness of calculating the prostate cancer immunoscore in a small, preliminary panel of African American and Caucasian patients from our tissue bank. In our Specific Aim 2, we will determine the prostate cancer immunoscore and androgen receptor status in a large cohort of African American (1,630) and Caucasian (1,630) patients, for which we also have 10-year follow-up data. We will then be able to determine if differences exist between African Americans and Caucasians with respect to: prostate cancer immunoscores, the spectrum/quantity of tumor-infiltrating T lymphocytes (CD3+, CD4+, and CD8+), and/or androgen receptor status; and if race is predictive of any of these variables. In our Specific Aim 3, we will perform Cox regression analysis and statistical modeling to determine if the prostate cancer immunoscore and/or AR status are predictors of long-term clinical outcomes (biochemical recurrence and/or disease-specific mortality) in African American and/or Caucasian patients with localized prostate cancer. If so, we will be able to construct an immunoscore-based classifier that clinicians can use to better predict outcome in their African American patients with prostate cancer-something that currently doesn't exist and is desperately needed. This work will also provide the clinical justification for future mechanisti studies surrounding race, tumor-infiltrating T lymphocytes, and androgen signaling in prostate cancer.